Exploration of anatomical distribution of brain metastasis from breast cancer at first diagnosis assisted by artificial intelligence.

Objectives: This study aimed to explore the spatial distribution of brain metastases (BMs) from breast cancer (BC) and to identify the high-risk sub-structures in BMs that are involved at first diagnosis. Methods: Magnetic resonance imaging (MRI) scans were retrospectively reviewed at our centre. The brain was divided into eight regions according to its anatomy and function, and the volume of each region was calculated. The identification and volume calculation of metastatic brain lesions were accomplished using an automatically segmented 3D BUC-Net model. The observed and expected rates of BMs were compared using 2-tailed proportional hypothesis testing. Results: A total of 250 patients with BC who presented with 1694 BMs were retrospectively identified. The overall observed incidences of the substructures were as follows: cerebellum, 42.1 %; frontal lobe, 20.1 %; occipital lobe, 9.7 %; temporal lobe, 8.0 %; parietal lobe, 13.1 %; thalamus, 4.7 %; brainstem, 0.9 %; and hippocampus, 1.3 %. Compared with the expected rate based on the volume of different brain regions, the cerebellum, occipital lobe, and thalamus were identified as higher risk regions for BMs (P value ≤ 5.6*10-3). Sub-group analysis according to the type of BC indicated that patients with triple-negative BC had a high risk of involvement of the hippocampus and brainstem. Conclusions: Among patients with BC, the cerebellum, occipital lobe and thalamus were identified as higher-risk regions than expected for BMs. The brainstem and hippocampus were high-risk areas of the BMs in triple negative breast cancer. However, further validation of this conclusion requires a larger sample size.

Screening and functional analysis of StMYB transcription factors in pigmented potato under low-temperature treatment.

MYB transcription factors play an extremely important regulatory role in plant responses to stress and anthocyanin synthesis. Cloning of potato StMYB-related genes can provide a theoretical basis for the genetic improvement of pigmented potatoes. In this study, two MYB transcription factors, StMYB113 and StMYB308, possibly related to anthocyanin synthesis, were screened under low-temperature conditions based on the low-temperature-responsive potato StMYB genes family analysis obtained by transcriptome sequencing. By analyzed the protein properties and promoters of StMYB113 and StMYB308 and their relative expression levels at different low-temperature treatment periods, it is speculated that StMYB113 and StMYB308 can be expressed in response to low temperature and can promote anthocyanin synthesis. The overexpression vectors of StMYB113 and StMYB308 were constructed for transient transformation tobacco. Color changes were observed, and the expression levels of the structural genes of tobacco anthocyanin synthesis were determined. The results showed that StMYB113 lacking the complete MYB domain could not promote the accumulation of tobacco anthocyanins, while StMYB308 could significantly promote the accumulation involved in tobacco anthocyanins. This study provides a theoretical reference for further study of the mechanism of StMYB113 and StMYB308 transcription factors in potato anthocyanin synthesis.

Identification of a Difluorinated Alkoxy Sulfonyl Chloride as a Novel Antitumor Agent for Hepatocellular Carcinoma through Activating Fumarate Hydratase Activity.

Fenofibrate is known as a lipid-lowering drug. Although previous studies have reported that fenofibrate exhibits potential antitumor activities, IC50 values of fenofibrate could be as high as 200 µM. Therefore, we investigated the antitumor activities of six synthesized fenofibrate derivatives. We discovered that one compound, SIOC-XJC-SF02, showed significant antiproliferative activity on human hepatocellular carcinoma (HCC) HCCLM3 cells and HepG2 cells (the IC50 values were 4.011 µM and 10.908 µM, respectively). We also found this compound could inhibit the migration of human HCC cells. Transmission electron microscope and flow cytometry assays demonstrated that this compound could induce apoptosis of human HCC cells. The potential binding sites of this compound acting on human HCC cells were identified by mass spectrometry-cellular thermal shift assay (MS-CETSA). Molecular docking, Western blot, and enzyme activity assay-validated binding sites in human HCC cells. The results showed that fumarate hydratase may be a potential binding site of this compound, exerting antitumor effects. A xenograft model in nude mice demonstrated the anti-liver cancer activity and the mechanism of action of this compound. These findings indicated that the antitumor effect of this compound may act via activating fumarate hydratase, and this compound may be a promising antitumor candidate for further investigation.

Association between Left Ventricular Longitudinal Strain (GLS) and Prognosis of the Patients Undergoing Heart Valve Surgery with Preserved Left Ventricular Ejection Fraction.

PURPOSE: Global longitudinal strain (GLS) seems accurate for detecting subclinical myocardial dysfunction. This study aimed to determine the association between GLS and postoperative intensity of inotropic support in the patients undergoing heart valve surgery with preserved left ventricular ejection fraction. METHODS: 74 patients with preserved left ventricular ejection fraction who underwent valve surgery during the period between March 2021 and June 2022 were included in this prospective observational study. Transthoracic echocardiography including strain analysis with speckle tracking was performed before surgery. Patients were stratified according to the left ventricle (LV) GLS: LV-GLS ≥-16% (Impaired GLS group) and LV-GLS <-16% (Normal GLS group). The primary endpoint was postoperative vasoactive inotropic score. A high vasoactive inotropic score (VIS) was defined as a maximum VIS of ≥15 within 24 hours postoperatively. Postoperative adverse events, baseline clinical and echocardiographic data were also recorded. We invested the ability of preoperative GLS in predicting adverse postoperative outcomes, such as prolonged mechanical ventilation and the need for pharmacologic hemodynamic support after cardiac surgery. RESULTS: Seventy-four patients were included and analyzed in this study, including thirty-three in impaired GLS group and forty-one in normal GLS group. In-hospital mortality was 1.27% (1/74). Patients in impaired GLS group were more likely to have prolonged mechanical ventilation (p = 0.041). Multivariable logistic regression analysis revealed that the apical four-chamber view of the left ventricle (A4C)-GLS was significantly associated with high VIS (OR 1.373, p = 0.007). A4C-GLS had a sensitivity of 62.5% and a specificity of 89.66% for predicting high VIS (area under the curve, 0.78). The relationships between GLS and other secondary outcome measures were not statistically significant. The optimal cutoff of A4C-GLS for postoperative high vasoactive inotropic score was -10.85%. CONCLUSION: Preoperative LV dysfunction is an independent risk factor for postoperative high VIS. A4C-GLS may be a reliable tool in predicting high VIS after cardiac surgery. Those patients with impaired contractility were at high risk for elevated inotropic support and prolonged mechanical ventilation after cardiac surgery. These findings suggest an important role for echocardiographic GLS in perioperative assessment of cardiac function in the patients undergoing cardiac surgery.

Evidence and possible mechanism of Scutellaria baicalensis and its bioactive compounds for hepatocellular carcinoma treatment.

BACKGROUND: Traditional Chinese medicines have been reported to have outstanding effects in the treating of hepatocellular carcinoma. Scutellaria baicalensis (S. baicalensis) has demonstrated anti-tumor, anti-angiogenic, and anti-inflammatory properties. Baicalein, wogonin, and baicalin are the main pharmacologically bioactive compounds of S. baicalensis. METHODS: Eight electronic databases were searched to select articles published from their inception to 30 May 2022. For selected articles, clinical and preclinical data was obtained on the use of S. baicalensis and its bioactive compounds in hepatocellular carcinoma therapy. Statistical analyses were performed using RevMan version 5.3 and Stata software. Quality assessment of the studies was performed using Cochrane and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)'s risk of bias tools. RESULTS: Seven clinical and 17 preclinical in vivo studies along with 31 in vitro studies were included in this research. Meta-analysis showed that a Chinese herbal medicine preparation, with S. baicalensis as the sovereign herb, combined with Transcatheter arterial chemoembolization (TACE) or primary treatment, could lead to a significantly improved tumor objective response rate (Risk ratio (RR) = 1.57, 95% confidence interval (CI): [1.30, 1.90], p < 0.00001). Scutellaria baicalensis-based extracts (standard mean difference (SMD) = -0.86, 95%CI: [-1.20, -0.53], p < 0.00001), baicalein (SMD = -4.80, 95%CI: [-6.66, - 2.95], p < 0.00001), baicalin (SMD = -2.28, 95%CI [-3.26, -1.30], p < 0.00001) and wogonin (SMD = -1.41, 95%CI [-2.26, -0.57], p < 0.00001) slowed tumor growth in vivo. These outcomes might be linked to the mechanism by which S. baicalensis promotes apoptosis, induces autophagy, and blocks the expression of vascular endothelial growth factor (p < 0.05). CONCLUSION: Based on experimental and clinical evidence, we believe that S. baicalensis and its bioactive compounds have therapeutic potential and plausible mechanisms of action against hepatocellular carcinoma, in terms of efficacy and safety.